Immunomodulatory Therapy for Neuropathic Pain

神经性疼痛的免疫调节疗法

基本信息

  • 批准号:
    10490450
  • 负责人:
  • 金额:
    $ 92.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Principal Investigator/Program Director (Last, First, Middle: Ridong Chen Project Summary More than 25 million Americans suffer from chronic pain. Due to the lack of other treatments, there has been an overreliance on opioids, contributing to an alarming epidemic of opioid overdose addictions and deaths. Neu- ropathic pain is difficult to treat, with only 30-40% of patients achieving meaningful (>40-50%) pain relief. Current therapies (e.g., duloxeline and gabapentin) mainly address symptoms by focusing on blocking neurotransmis- sion in the pain pathway with limited efficacy, severe side effects, and narrow therapeutic indices. Hence, novel non-opioid therapies are urgently needed to safely manage symptoms and also target the underlying pathophys- iological mechanisms that will improve the functional status and quality of life of affected patients. It has been recently shown that CD4+ Th1 is a major player for neuropathic pain development. Interleukin-2 (IL-2) is the key cytokine for the generation, survival, and function of regulatory T cells by direct binding to its high affinity receptor. Treatment with low-dose rIL-2 increased anti-inflammatory regulatory T cells and M2 type macrophages and inhibited pathogenic interferon- secreting T helper type 1 cells. This rIL-2 treatment was efficacious in human clinical studies for autoimmune diseases without complications or infections. Hence, resto- ration or enhancement of regulatory T cells with low-dose IL2 may offer a novel strategy for prevention and treatment of neuropathic pain. However, several drawbacks exist for current low-dose rIL2 therapy, including a short half-life, propensity for in vitro aggregation causing adverse local reaction at injection sites, and a potential narrow therapeutic window. We have designed proprietary IL2-based variants that will enable selective stimu- lation of Tregs with an extended half-life and a broad therapeutic window. In the Phase I study, we successfully identified the variant, designated APT603, which selectively stimulates regulatory T cells and provides robust analgesic efficacy in the chronic constriction injury model of mononeuropathy in rats with an excellent safety profile. With an experienced drug development team, we propose to determine dose responses in two well es- tablished models of neuropathic pain with distinct pathophysiology and to conduct critical activities necessary to enable IND filing for APT603.  Specific Aim 1: Determine the therapeutic index of APT603 for abrogating neuropathic pain in STE- induced (T1D) diabetic rats and in a rat model of sciatic nerve chronic constriction injury (CCI).  Specific Aim 2: Manufacture cGMP (Current Good Manufacturing Practice) grade APT603.  Specific Aim 3: Evaluate the nonclinical safety of APT603. The long-term goal is to develop the drug candidate as a safe and disease-modifying analgesic therapy. Weekly or bi-weekly dosing will provide sustained neuropathic pain relief for patients without inducing significant side effects, tolerance, or addiction.
首席研究员/项目总监(倒数第一中:陈日东

项目成果

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RIDONG CHEN其他文献

RIDONG CHEN的其他文献

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{{ truncateString('RIDONG CHEN', 18)}}的其他基金

Multi-functional anti-thrombotic therapy for coronary microvascular obstruction
多功能抗血栓治疗冠状动脉微血管阻塞
  • 批准号:
    10696319
  • 财政年份:
    2023
  • 资助金额:
    $ 92.25万
  • 项目类别:
Peripherally Acting Analgesic for Osteoarthritis Pain
用于治疗骨关节炎疼痛的外周镇痛药
  • 批准号:
    10249564
  • 财政年份:
    2021
  • 资助金额:
    $ 92.25万
  • 项目类别:
Synergistic Efficacy of an Interleukin 2 Analog and Antitumor Antigen Antibody
白细胞介素 2 类似物和抗肿瘤抗原抗体的协同功效
  • 批准号:
    9905448
  • 财政年份:
    2019
  • 资助金额:
    $ 92.25万
  • 项目类别:
Immunomodulatory Therapy for Neuropathic Pain
神经性疼痛的免疫调节疗法
  • 批准号:
    10684821
  • 财政年份:
    2018
  • 资助金额:
    $ 92.25万
  • 项目类别:
Immunomodulatory Therapy for Neuropathic Pain
神经性疼痛的免疫调节疗法
  • 批准号:
    10378231
  • 财政年份:
    2018
  • 资助金额:
    $ 92.25万
  • 项目类别:
IL2-based Immunotherapy for Type 2 Diabetes
基于 IL2 的 2 型糖尿病免疫疗法
  • 批准号:
    9135661
  • 财政年份:
    2016
  • 资助金额:
    $ 92.25万
  • 项目类别:
IL2-based Immunotherapy for Lupus
基于 IL2 的狼疮免疫疗法
  • 批准号:
    9253700
  • 财政年份:
    2016
  • 资助金额:
    $ 92.25万
  • 项目类别:
Low-dose IL-2-based Immunomodulatory Therapy for PAH
基于低剂量 IL-2 的 PAH 免疫调节疗法
  • 批准号:
    8829630
  • 财政年份:
    2015
  • 资助金额:
    $ 92.25万
  • 项目类别:
Human Apyrase Therapy for Diabetic Neuropathic Pain
人腺苷三磷酸双磷酸酶治疗糖尿病神经性疼痛
  • 批准号:
    8976658
  • 财政年份:
    2015
  • 资助金额:
    $ 92.25万
  • 项目类别:
Manufacturing of Growth Factors to Enable Cardiopoietic Stem Cell Therapy for Hea
制造生长因子以实现心脏造血干细胞治疗
  • 批准号:
    8766958
  • 财政年份:
    2014
  • 资助金额:
    $ 92.25万
  • 项目类别:

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